title: A phase 2 study of intravenous panobinostat in patients with castration-resistant prostate cancer.
abstract: OBJECTIVE
  Panobinostat, a pan-deacetylase inhibitor, increases acetylation of proteins associated with growth and survival of malignant cells. This phase 2 study evaluated the efficacy of intravenous (IV) panobinostat in patients with castration-resistant prostate cancer (CRPC) who had previously received chemotherapy. The primary end point was 24-week progression-free survival. Secondary end points included safety, tolerability, and the proportion of patients with a prostate-specific antigen (PSA) decline.
  
  
  METHODS
  IV panobinostat (20 mg/m(2)) was administered to patients on days 1 and 8 of a 21-day cycle. Tumor response was assessed by imaging every 12 weeks (4 cycles) according to modified response evaluation criteria in solid tumors (Scher et al. in Clin Cancer Res 11:5223-5232, 23), and PSA response was defined as a 50 % decrease from baseline maintained for ≥4 weeks. Safety monitoring was routinely performed and included electrocardiogram monitoring.
  
  
  RESULTS
  Of 35 enrolled patients, four (11.4 %) were alive without progression of disease at 24 weeks. PSA was evaluated in 34 (97.1 %) patients: five (14.3 %) patients demonstrated a decrease in PSA but none ≥50 %; one patient (2.9 %) had carcinoembryonic antigen as a marker of his prostate cancer, which declined by 43 %. Toxicities regardless of relationship to panobinostat included fatigue (62.9 %), thrombocytopenia (45.7 %), nausea (51.4 %), and decreased appetite (37.1 %).
  
  
  CONCLUSIONS
  Despite promising preclinical data and scientific rationale, treatment with IV panobinostat did not show a sufficient level of clinical activity to pursue further investigation as a single agent in CRPC.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA. rathkopd@mskcc.org
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
authors.forename: Susan
authors.initials: S
authors.lastname: Ellard
authors.forename: Kim Nguyen
authors.initials: KN
authors.lastname: Chi
authors.forename: Thomas
authors.initials: T
authors.lastname: Nydam
authors.forename: Erin
authors.initials: E
authors.lastname: Allen-Freda
authors.forename: Kaushal Kishor
authors.initials: KK
authors.lastname: Mishra
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Porro
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: George
authors.initials: G
authors.lastname: Wilding
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D000077767:Panobinostat; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat; D017430:Prostate-Specific Antigen